Esophageal Cancer. Wesley A. Papenfuss MD FACS Surgical Oncology Aurora Cancer Care. David Demos MD Thoracic Surgery Aurora Cancer Care

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1 Esophageal Cancer Wesley A. Papenfuss MD FACS Surgical Oncology Aurora Cancer Care David Demos MD Thoracic Surgery Aurora Cancer Care

2 No Disclosures

3 Learning Objectives Review the classification scheme for GE junction cancers Review workup and evaluation Review Minimally Invasive Esophagectomy

4 Epidemiology Esophageal Cancer is 6 th leading cause of death worldwide Incidence has been rising in Western countries ~17,000 cases anticipated 2015 in US Adenocarcinoma 70% Obesity, GERD, Barretts Squamous Cell Carcinoma 30% Tobacco, Alcohol

5 Squam Esophageal Adeno Adeno Melanoma Prostate Breast/lung/ colon Distal 1/3 Pohl & Welch, JNCI 2005

6 Cancer at the GE Junction Siewart Classification I located in the distal 5 cm of esophagus, but does not cross GE junction II centered around the GE junction III greater than 5 cm distal to the GE junction Treated as Gastric Cancer Marriette, Lancet Onc 2011

7 Patient Examples of GE Junction Cancer Esophageal Cancer I/II Gastric Cancer III

8 Evaluation of the Esophageal Mass High quality endoscopy Defines the anatomic esophagogastric junction Describes the anatomic location Endoscopic ultrasound (EUS) Assessment of T-stage; Nodal involvement FNA of suspicious node CT / PET

9 Staging of Esophageal Cancer T Stage T1a : lamina propria, muscularis mucosa T1b : submucosa T2 : muscularis propria T3 : adventitia T4 : adjacent structures N Stage N1 : 1-2 nodes N2 : 3-6 nodes N3 : > 7 nodes J Thoracic Surg 2017

10 Accuracy of EUS for T Stage / Nodes Operator dependent Very good at early vs late (ie T1 vs T3/4) More difficult discerning between earlier lesions (ie T1a vs T1b vs T2) Review of 107 patients with early stage (Tis, T1) compared to final pathology Understaging: 30% of T1a 49% of T1b Overstaging: 29% of T1a 51% of T1b J Thor and Cardiovas Surg 2014

11 Risk of Nodal Disease Based on T stage Lymph node involvement greatest predictor of prognosis T stage is best predictor of lymph node involvement Squam us T1 T1a T1b T2 T3 T4 20% 0-3% 5-40% 40 % Adeno 10% 0-2% 0-40% 50 % 60 % 80 % 80 % 90 % Clin Endosc 2014

12 Staging Laparoscopy Used selectively in patient with Type II/III tumors Yield is variable (5%-30%) Extraluminal assessment of tumor location Evaluate future conduit Placement of feeding jejunostomy

13 Early Stage (T1, N0) Endoscopic Therapies for Tis or T1a EMR / ESD followed by ablation Esophagectomy Locally Advanced (T2 or N+) Neoadjuvant therapy Metastatic Definitive Chemotherapy

14 Endoscopic Therapies Endoscopic Mucosal Resection Endoscopic Submucosal Dissection Ablation of Surrounding Barrett s

15 Colorectalsurgeonsydney.com

16 Locally Advanced Disease T2 tumors N+ disease Neoadjuvant Chemotherapy & Radiation Paclitaxel and Carboplatin weekly x 5 weeks 50.4 Gy over 28 fractions

17 CROSS Trial Randomized patients to preop chemoxrt + surgery vs. surgery alone Carboplatin & Paclitaxel 41.4 Gy radiation over 23 fractions R0 resection rate (92% vs 69%) 29% complete pathologic response 23% adenocarcinoma 49% squamous Van Hagen, NEJM 2012

18 CROSS Trial

19 CROSS Patterns of Recurrence CRT had lower local recurrence rate Anastomosis: 2.8% vs 8.7% Mediastinum: 7.0% vs 20.5% CRT had lower distant recurrence rate Carcinomatosis: 4.2% vs 13.7% Hematogenous: 28.6% vs 35.4% No difference in Nodal recurrence Celiac, Periaortic, Supraclavicular Oppedijk et al. JCO :385

20 MAGIC Trial Evaluated Perioperative Chemotherapy vs Surgery Alone Gastric Cancer including the lower 1/3 of esophagus 25% were GE Jxn (11%) or Esophageal (14%) Epirubicin/Cisplatin/Fluoruracil 3 cycles preop / 3 cycles post op 86% of patients completed preop chemo 55% started post op chemo 41% of patients assigned to the chemotherapy group completed all 6 cycles

21 Cunningham et al, NEJM 2006

22 FLOT FLOT Fluorouracil / leucovorin Oxaliplatin Docetaxel Phase 3 FLOT 4 - abstract FLOT vs ECF/ ECX Improved OS (50 v 35 mo) Improved PFS (30 v 18 mo) Improved R0 Smaller tumors FLOT vs Cross Propensity matched study No survival benefit CRT had better tumor response, fewer nodes ESOPEC Randomizing pts to FLOT vs CROSS Opened 2016 Expected NCT ESMO 2017 Abs LBA27 Eur J Surg Onc 2017 BMC Cancer 2016

Neck Ivor Lewis Abdominal incision Right chest

23 Surgical Approaches to Esophagectomy Transhiatal Abdominal incision Neck incision Anastomosis in the Neck Ivor Lewis Abdominal incision Right chest incision Anastomosis in the Chest Minimally Invasive Esophagectomy

24 Marriette, Lancet Onc 2011

25 Comparison of Open Approaches Transhiatal % Ivor Lewis % P-Value Pneumonia NS Sepsis/Shock NS Return to OR Morbidity NS Serious Morbidity NS Mortality Papenfuss et al, J Surg Onc 2014

26 Minimally Invasive Esophagectomy Improvement in Morbidity Extent of Lymphadenectomy Multiple approaches described

27 >1000 MIE 48% Neck Anastomosis 52% Chest Anastomosis Neck Chest P value RLN 8% 1% <0.001 Leak 5% 4% 0.4 Mortality 2.5% 0.9% 0.08 Luketich, Ann Surg 2012

28 MIE vs Traditional Esophagectomy RCT of 115 patients to MIE (prone) vs Right Thoractomy, Laparotomy, Cervical incision > 90% had modern neoadjuvant chemoradiation: carboplatin, paclitaxel, XRT Significant difference in early postoperative pulmonary complications favoring MIE 34% vs 12% in hospital No difference in LN, RO, Mortality Bierre, Lancet 2012

29 - Single-institution retrospective study of 129 patients undergoing curative-intent esophagectomy for pt1 ESCC - Group 1 (n=42): standard MLND - Group 2 (n=87): Extensive MLND J Gastrointest Surg (2017)

30 The Aurora Approach THE TEEM Trans Hiatal Esophagectomy Transcervical Endoscopic Esophageal Mobilization **Da Vinci Xi Robot-Assisted

31 THE TEEM Approach - Aurora one of few centers around the world to use this technique - Combines the oncologic advantage of transthoracic approach with the morbidity advantage of the transhiatal approach

32 Video / Graphic

33 THE TEEM Operative Data Complications Year Author Country N Abdomen OR time No of LNs Pulmonary Leak RLN Palsy LOS 30d Mort 1993 Bumm Germany 30 Open 4 (13.3%) 6 (20%) 2 (6.6%) 2 (6.6%) 2004 Tangoku Japan (24.4%) 4 (9.8%) 15 (36.6%) 2010 Wu China 40 Open 32 (80%), Lap 8 (20%) (2.5%) 3 (7.5%) 2 (5%) Parker US (Mayo Florida) 8 Laparoscopic (25%) 2 (25%) Feng China 27 Open (26%) 5 (18%) 5 (18%) (3.7%) 2014 Wang China (5.7%) 5 (7.1%) 2 (2.9%) Okumura et al Japan 63 Open (6.3%) 14 (22.2%) 6 (11.5%) 1 (1.6%) 2016 Nomura Japan 20 Open Mori Japan 22 DaVinci S for mediastinum (18%) 1 (4.5%) Fujiwara Japan (6.7%) 9 (15%) 20 (33.3%) Aurora Health Care US Aurora N= min Time Afib Leak VC Pneum Bleed 30 d mort 37% 6% 15% 7% 7% 0 Bierre, Lancet 2012

34 Thank You

35 Management of Complete response for SCC Complete pathologic response is higher in SCC than Adeno Progression free survival is better in patients treated with surgery Overall survival is not improved Cancer specific survival was improved in surgery groups? High mortality rate in surgery arm (10%)

36 Roswell Park Experience 81 patients from Endoscopic resection of T1a patients Ablation of associated Barrett s 7 patients had T1b disease (all negative margins) 3.25 years of follow up 84% eradication of HGD One patient developed invasive carcinoma Treated endoscopically 100% cancer specific survival Nurkin, Surg End 2013

37 Human epidermal growth factor (HER2) Associated with cell proliferation Amplified in 10-25% of GE Jxn cancers Trastuzumab Monoclonal antibody to HER2

38 Trastuzumab for Gastric Cancer Study (ToGA) Compared Chemotherapy +/- trastuzumab Capecitabine/fluorouracil plus cisplatin Locally advanced or Metastatic Gastric/EGJ cancers Approximately 20% were EGJ Improvements in OS, PFS ToGA, Lancet 2010

39 ToGA, Lancet 2010

40 RTOG 1010 Evaluate the addition of Trastuzumab to Neoadjuvant therapy for GE Jxn cancer Carboplatin, Paclitaxel, XRT +/- trastuzumab Anticipated 480 Enrollees Local PI: Dr. Robert Behrens

Determining the Optimal Surgical Approach to Esophageal Cancer

Determining the Optimal Surgical Approach to Esophageal Cancer Amit Bhargava, MD Attending Thoracic Surgeon Department of Cardiovascular and Thoracic Surgery Open Esophagectomy versus Minimally Invasive